Highly accurate positioning is fundamental to the performance of microsurgery. Vitreoretinal microsurgery in particular is among the most demanding of specialties in terms of positioning accuracy, and is likely to become more so due to the increasing interest in retinal microvascular interventions. Of similar importance when dealing with delicate tissues is precise control of applied force. The lack of it leads to complications such as iatrogenic retinal breaks during membrane peeling. The original research period under this R01 grant was devoted to the basic development of a fully handheld micromanipulator that performs active tremor compensation by sensing its own movement and deflecting its tool tip to counteract the tremor. A full working prototype has been built and tested, and the tremor compensation has been demonstrated; the ground has now been laid for the realization of the fuller potential of this device for the control of both position and force, which may open the way to numerous significant clinical benefits: reducing complications, improving overall outcomes, and possibly enabling new types of procedures. This research aims to optimize the parameters of the new tremor compensation filter used within Micron, and validate its improved performance with human users in retinal vein cannulation in vitro in porcine cadaver eyes and in ovo in a chick chorioallantoic membrane (CAM) model, and in cell micromanipulation in the biology laboratory. Improved methods for semi automated micromanipulation with Micron will then be developed and validated with human users in patterned laser photocoagulation in vitro and in chick CAM. Methods for force control of Micron will then be developed and validated with human users in membrane peeling and retinal vessel cannulation tasks in vitro and in chick CAM. The active tremor compensation will be tested primarily in cannulation, the scanning technique in patterned laser photocoagulation, and the force control in membrane peeling and vessel cannulation.